Lateral Gene Transfer and Antibiotic Resistance of Shigella
Lateral gene transfer has an integral roll in the evolution of bacteria and contributes to is diversity. Until the 1950's little was known about lateral gene transfer and how significant a role it played in antibiotic resistance. Due to the fact many different types of bacteria were becoming resistance to the same antibiotic it indicated that the resistance was being transferred from one type of bacteria to another 1. Lateral Gene Transfer Molecular genetic analysis of DNA sequences can identify the evolutionary history of genes within a region of bacterial DNA. That region of DNA can be compared to the ancestral genes that are vertically transmitted to see if it indeed was a lateral gene transfer. This is because the sequence that is new to the bacterial genome retains the sequence of the donor genome and therefore can be distinguished from the ancestral DNA 1.  Lateral gene transfer requires three event to occur. There needs to be a way for the donor DNA to be delivered to the recipient cell. This can occur through transduction, transformation, or conjugation. The acquired sequence then has to be incorporated into the recipient cells genome. Finally the incorporated DNA must be expressed in a way that befits the recipient cell 1. Antibiotic Resistance Antibiotic resistance is a way for microorganisms to expand their niche. By acquiring a resistance they are able to proliferate around noxious elements. The most common way microorganism acquire an antibiotic resistance is through the mobilization of plasmids (ie. virulence plasmids) between taxa. Another way is through transposable elements 1. Shigella sp. Shigella sp. is a type of bacteria that originated from E. coli. It was formed when E.coli acquired SHI-1 and SHI-2 as well as a virulence plasmic through lateral gene transfer from a unknown source. The E.coli genome contains ompT, a gene that interferes with the expression of Shigella ''VirG protein thereby stopping the spread of the protein, and contains cadA, which normally encode lysine decarboxylase. Both the opt and the cadA are absent in ''Shigella 1.   Shigella is a gram negative enteric bacteria. There are four known species S. dysenteriae, S. flexneri, S. boydii, ''and ''S. sonnei. It invades a human host through the colonic and rectal epithelium after a person ingests contaminated water. It enters the epithelium through M Cells in the follicle-associated epithelium, which cover lymph nodes in the mucosa. It can then infect neighboring cells through their tight junctions. The result is the disease Shigellosis or bacillary dysentery 2.   Bacillary dysentery kills over 1.1 million people per year. People become infected through a fecal-oral route which is common in contaiminated water. To treat the disease people have to be rehydrated because the most common symptom is violent diarrhea. Infected people will then be treated with antimicrobial therapy. This treatment has been proven to be harder and harder because antimicrobial therapy is so widely used and bacteria have more oportunity to acquire a resistance to the antibiotics 3.   In the 1950's people found that Shigella was resistant to many antibiotics. Since this first discovey many multi-resistant gene clusters on R-plasmids, integrons, and transposons have been identified 3.   The most interesting of these gene clusters are those on the virulent plasmid called pathogenicity islands 5. Pathogenicity Islands (PAI) It has been found that the ''S. flexneri ''genome has a chromosome as well as smaller DNA structures called a virulence plasmid. This virulence plasmid contains genes called pathogenicity islands, which cause disease in people affected with the bacterium 5. Pathogenicity islands (PAI) are highly mobile between different species of bacteria and are believe to be acquired by lateral gene transfer. They carry phage related integrase genes, are integrated into tRNA genes, are flanked by short direct repeats, and carry mobile elements like insertion sequences and transposons 3.   So far 64 PAI have been identified and scientists are continually trying to find what percent of the PAI's are involved in the virulence the bacteria S. flexneri 5. In a study by Turner SA, et al. (2003), Shigella resistance locus (SRL) were found to be carried on PAI's. This particular loci enables the Shigella speice to become resistant to the antibiotics tetracycline, chloramphenicol, ampicillin, and streptomycin when in their presence 3,6. In 2001, a study by Luck S.N. et al., found the first example of an Iron transport system within a Pathogenicity islands (PAI) on Shigella flexneri 2a YSH6000. The Iron on the PAI is for that survival of the bacteria and plays a role in bacterial virulence 4. This study identified a ferric uptake system (Fec) is encoded by the previously discovered Shigella resistance locus (SRL) on the PAI. This however is not the only Iron uptake system in the S. flexneri because when they inhibited the gene in the bacteria it was still able to grown a iron-limited media. They sequenced the DNA of the bacteria and found that the fec is linked to the SRL and both are integrated into the tRNA gene 4. References 1. Ochman H, Lawreance JG, Grolsman EA. 2000. Lateral gene transfer and the nature of bacterial innovation. Nature. 205: 299-303. Link: http://classes.biology.ucsd.edu/bimm120.SP07/Lecture12review.pdf 2. Virulence Factors of Pathogenic Bacteria. 2003. State Key Laboratory for Moleclular Virology and Genetic Engineering,Bejing, China. Link: http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Shigella 3. Turner SA, Luck SN, Sakellaris H, Rajakumar K, Adler B. 2004. Role of attP in Integrase-Mediated Integration of the Shigella Resistance Locs Pathogenicity Island of Shigella flexneri. Antimicrobial Agents Chemotherapy. 48930: 1028-1031. Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC353151/ 4. Luck SN, Turner SA, Rajakumar K, Sakellaris H, Adler B. 2001. Ferric dictate transport system ( Fec) of Shigella flexneri 2a YSH6000 is encoded on a novel pathogenicity island carrying multiple antibiotic resistance genes. Infect Immunity. 69(10):6012-21. Link: http://www.ncbi.nlm.nih.gov/pubmed/11553538 5. Reinert B. Infant mortality: New clues from the sequenced Shigella genome. Genome News Network. Nov. 8 2002. Link: http://www.genomenewsnetwork.org/articles/11_02/shigella.shtml 6. Turner SA, Luck SN, Sakellaris H, Rajakumar K, Adler B. 2003. Molecular epidemiology of the SRL pathogenicity island. Antimicrobial Agents Chemotherapy. 47(2): 727-34. http://www.ncbi.nlm.nih.gov/pubmed/12543684/  